BACKGROUND We report data from stage 1 of an ongoing 2-staged, phase 1/2 randomized clinical trial with a 4-component generalized modules for membrane antigens-based vaccine against Shigella sonnei and Shigella flexneri 1b, 2a, and 3a (altSonflex1-2-3; GSK). METHODS Europeans aged 18-50 years (N = 102) were randomized (2:1) to receive 2 injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at prespecified time points. RESULTS The most common solicited administration-site event (until 7 days after each injection) and unsolicited adverse event (until 28 days after each injection) were pain (altSonflex1-2-3, 97.1%; placebo, 58.8%) and headache (32.4%; 23.5%), respectively. All serotype-specific functional IgG antibodies peaked 14-28 days after injection 1 and remained substantially higher than prevaccination at 3 or 6 months postvaccination; the second injection did not boost but restored the initial immune response. The highest seroresponse rates (≥4-fold increase in titers over baseline) were obtained against S. flexneri 2a (enzyme-linked immunosorbent assay [ELISA] after injection 1, 91.0%; after injection 2 [day 113; day 197], 100%; 97.0% and serum bactericidal activity [SBA] after injection 1, 94.4%; after injection 2, 85.7%; 88.9%) followed by S. sonnei (ELISA after injection 1, 77.6%; after injection 2, 84.6%; 78.8% and SBA after injection 1, 83.3%; after injection 2, 71.4%; 88.9%). Immune responses against S. flexneri 1b and S. flexneri 3a, as measured by both ELISA and SBA, were numerically lower compared to those against S. sonnei and S. flexneri 2a. CONCLUSIONS No safety signals or concerns were identified. altSonflex1-2-3 induced functional serotype-specific immune responses, allowing further clinical development in the target population. Clinical Trials Registration . NCT05073003.

中文翻译：

---

用于膜抗原志贺氏菌疫苗的 4 组分广义模块在健康欧洲成人中的安全性和免疫原性：随机、1/2 期研究。


背景 我们报告了一项正在进行的 2 阶段、1/2 期随机临床试验的第 1 阶段数据，该试验使用针对 Shigella sonnei 和 Shigella flexneri 1b、2a 和 3a 的基于膜抗原的疫苗的 4 组分广义模块（altSonflex1-2-3;GSK）。方法 年龄在 18-50 岁之间 （N = 102） 的欧洲人被随机分配 （2：1） 接受 2 次 altSonflex1-2-3 或安慰剂注射，间隔 3 个月或 6 个月。在预先指定的时间点评估安全性和免疫原性。结果最常见的主动给药部位事件（每次注射后 7 天）和主动不良事件（每次注射后 28 天）分别为疼痛 （altSonflex1-2-3， 97.1%;安慰剂 58.8%） 和头痛 （32.4%;23.5%）。所有血清型特异性功能性 IgG 抗体在注射 1 后 14-28 天达到峰值，并在接种后 3 或 6 个月仍显著高于接种前;第二次注射没有增强，但恢复了最初的免疫反应。福氏血吸虫 2a 的血清反应率最高（滴度比基线增加 ≥4 倍）（注射 1 后酶联免疫吸附测定 [ELISA]，91.0%;注射 2 后 [第 113 天;第 197 天]，100%;注射 1 后 97.0% 和血清杀菌活性 [SBA]，94.4%;注射 2 后，85.7%;88.9%），其次是 S. sonnei（注射 1 后 ELISA，77.6%;注射 2 后，100%; 84.6%;78.8% 和注射后 SBA 1,83.3%;注射后 2 ，71.4%;88.9%).通过 ELISA 和 SBA 测量的针对 S. flexneri 1b 和 S. flexneri 3a 的免疫反应在数值上低于针对 S. sonnei 和 S. flexneri 2a 的免疫反应。结论 未发现安全信号或担忧。 altSonflex1-2-3 诱导功能性血清型特异性免疫反应，允许在目标人群中进一步进行临床开发。临床试验注册 .NCT05073003。